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 Cellular Organisation and Signalling

R A G H U   P A D I N J A T 
 
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Presently two experimental systems are in use within the lab:

 

Drosophila photoreceptors

We study sensory transduction in Drosophila photoreceptors. These cells utilize G-protein coupled PLC activity for sensory transduction and offer a number of specific advantages for our work. In addition to being tractable to sophisticated molecular genetics, the sensory transduction cascade in fly photoreceptors uses G-protein coupled phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2] turnover to transduce the detection of light (Hardie and Raghu,  Nature 2001) and under conditions of bright light these cells experience high levels of PLCb activity but see limited depletion of plasma membrane PI(4,5)P2. Thus photoreceptors offer an excellent system to study the regulation of plasma membrane PI(4,5)P2 levels. We are using a combination of molecular genetics, live-cell imaging and electrophysiology to study Drosophila photoreceptors.

The rhabdomere, the light-sensing organ of Drosophila photoreceptors is the dramatically expanded apical domain of a polarized cell. It offers an excellent model to study questions related to the regulation of vesicular transport. We have previously used this system to discover a role for the lipid phosphatidic acid in regulating membrane transport (Raghu et.al J. Cell. Biol 2009)






 

 

Drosophila larval growth

During development Drosophila larvae undergo a dramatic increase in body size (2 log units increase over 96 hrs). This dramatic increase in body size is regulated by a number of signalling pathways including Insulin signalling. Previously we have used this system to discover novel roles for an ion channel, dTRPM (Georgiev, et.al, Cell Metabolism, 2010) and a lipid kinase (Gupta et.al Proc. Natl. Acad. Sci. USA 2013) is regulating growth and cell size.


Selected Publications

  • Gupta, A, Sarah Toscano, S, Trivedi, D, Jones DJ, Mathre S, Clarke J, Georgiev P, Divecha N and Raghu P. (2013) Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signalling and cell growth during Drosophila development. (Proc.Natl.Acad.Sci.USA published ahead of print March 25, 2013, doi:10.1073/pnas.1219333110).


  • Georgiev P, Okkenhaug H, Drews A, Wright D, Lambert S, Flick M, Carta V, Martel C, Oberwinkler J, Raghu P. (2010). TRPM channels mediate zinc homeostasis and cellular growth during Drosophila larval development. Cell Metab. 12(4):386-97.


  • Raghu, P., Coessens, E., Manifava, M., Georgiev, P., Pettitt, T., Wood, E., Garcia-Murillas, I., Okkenhaug, H., Trivedi, D., Zhang, Q., et al. (2009). Rhabdomere biogenesis in Drosophila photoreceptors is acutely sensitive to phosphatidic acid levels. J Cell Biol 185, 129-145.


  • Garcia-Murillas I, Pettit T, Macdonald E, Okkenhaug H, Georgiev P, Trivedi D, Hassan B, Wakelam M and Raghu, P (2006) lazaro encodes a lipid phosphate phosphohydrolase that regulates phosphatidylinositol turnover during Drosophila phototransduction. Neuron. 29:4, 533-546.


  • Hardie, R.C., and Raghu, P. (2001). Visual transduction in Drosophila. Nature 413, 186-193.